Atopic dermatitis and cytokines: Recent patents in immunoregulatory and therapeutic implications of cytokines in atopic dermatitis - part I: Cytokines in atopic dermatitis

Recent Patents on Inflammation and Allergy Drug Discovery

Volumn 6, Issue 3, 2012, Pages 222-247

  Lee, JaeHo ^a   Noh, Geunwoong ^b   Lee, Soojin ^c   Youn, YouSook ^d   Rhim, JungWoo ^d  

^a Chungnam National University   (South Korea)

^b Chungnam National University College of Medicine   (South Korea)

^c Eulji University   (South Korea)

^d The Catholic University of Korea   (South Korea)

Author keywords

Atopic dermatitis; Cytokine; Effector phase; Sensitization phase; Th2 polarization

Indexed keywords

CORTICOSTEROID; CYTOKINE; FOOD ALLERGEN; GAMMA INTERFERON; IMMUNOGLOBULIN E; INTERLEUKIN 12 ANTIBODY; INTERLEUKIN 13; INTERLEUKIN 16; INTERLEUKIN 17; INTERLEUKIN 21; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 31; INTERLEUKIN 33; INTERLEUKIN 35; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 9; SUPERANTIGEN; THYMIC STROMAL LYMPHOPOIETIN; TRANSFORMING GROWTH FACTOR BETA;

ATOPIC DERMATITIS; CELL DIFFERENTIATION; DENDRITIC CELL; DERMATITIS; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; EOSINOPHIL; FOOD ALLERGY; GENETIC VARIABILITY; HOUSE DUST; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL MEMORY; IMMUNOPATHOGENESIS; IMMUNOREGULATION; KERATINOCYTE; LANGERHANS CELL; NATURAL KILLER CELL; NEUTROPHIL; NONHUMAN; PATENT; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SENSITIZATION; STAPHYLOCOCCUS AUREUS; TH1 CELL; TH1 TH2 BALANCE; TH2 CELL;

ALLERGENS; ANIMALS; CYTOKINES; DERMATITIS, ATOPIC; HUMANS; IMMUNOGLOBULIN E; INFLAMMATION; PATENTS AS TOPIC;

EID: 84866640783     PISSN: 1872213X     EISSN: None     Source Type: Journal    
DOI: 10.2174/187221312802652820     Document Type: Review

References (323)

1. Oyoshi MK, He R, Kumar L, Yoon J, Geha RS. Cellular and molecularmechanisms in atopic dermatitis. Adv Immunol 2009; 102:135-226.
2. Leung DY. Atopic dermatitis: New insights and opportunities fortherapeutic intervention. J Allergy Clin Immunol 2000; 105: 860-76.
3. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest 2004; 113(5):651-7.
4. Sohn MH, Lee KE, Kim KE. Interleukin-18 is associated withincreased severity of atopic dermatitis in children. Allergy AsthmaProc 2004; 25: 181-4.
5. Novak N, Bieber T. Allergic and non allergic forms of atopic diseases. J Allergy Clin Immunol 2003; 112: 252-62.
6. Sicherer SH, Sampson HA. Food hypersensitivity and atopic dermatitis:Pathophysiology, epidemiology, diagnosis, and management. J Allergy Clin Immunol 1999; 104: S114-22.
7. Lack G, Fox D, Northstone K, Golding J. Factors associated withthe development of peanut allergy in childhood. N Engl J Med2003; 348: 977-85.
8. Worth A, Sheikh A. Food allergy and atopic eczema. Curr OpinAllergy Clini Immunol 2010; 10: 226-30.
9. Rancé F, Boguniewicz M, Lau S. New visions for atopic eczema:an Ipac summary and future trends. Pediatr Allergy Immunol 2008;19 (Suppl 19): 17-25.
10. Lee JH, Noh G, Noh J, Lee S, Choi WS, Lee K, et al. Clinicalcharacteristics of oral tolerance induction of IgE-mediated and non-IgE-mediated food allergy using IFN-gamma. Allergy Asthma Proc2010; 31: e39-e47.
11. Jujo K, Renz H, Abe J, Gelfand EW, Leung DYM. Decreasedinterferon gamma and increased interleukin-4 production in atopicdermatitis promotes IgE synthesis. J Allergy Clin lmmunol 1992;90: 323-31.
12. Hoffjan S, Epplen JT. The genetics of atopic dermatitis: Recentfindings and future options. J Mol Med 2005; 83: 682-92.
13. Maintz L, Novak N. Getting more and more complex: the pathophysiologyof atopic eczema. Eur J Dermatol 2007; 17: 267-83.
14. Grammatikos AP. The genetic and environmental basis of atopicdiseases. Ann Med 2008; 40(7): 482-95.
15. Zitnik SE, Rüschendorf F, Müller S, Sengler C, Lee YA, GriffioenRW, et al. Pediatr. IL13 variants are associated with total serumIgE and early sensitization to food allergens in children with atopicdermatitis. Allergy Immunol 2009; 20(6): 551-5.
16. Novak N, Kruse S, Kraft S, Geiger E, Kluken H, Fimmers R, et al. Dichotomic nature of atopic dermatitis reflected by combinedanalysis of monocyte immunophenotyping and single nucleotidepolymorphisms of the interleukin-4/interleukin-13 receptor gene:The dichotomy of extrinsic and intrinsic atopic dermatitis. J InvestDermatol 2002; 119: 870-5.
17. Kruse S, Japha T, Tedner M, Sparholt SH, Forster J, Kuehr J, et al. The polymorphisms S503P and Q576R in the interleukin-4 receptoralpha gene are associated with atopy and influence the signal transduction. Immunology 1999; 96: 365-71.
18. Namkung J-H, Lee J-E, Kim E, Park GT, Yang HS, Jang HY, et al. An association between IL-9 and IL-9 receptor gene polymorphismsand atopic dermatitis in a Korean population. J DermatolSci 2011; 62: 16-21.
19. Tsunemi Y, Saeki H, Nakamura K, Sekiya T, Hirai K, Fujita H, et al. Interleukin-12 p40 gene (IL12B) 30-untranslated regionpolymorphism is associated with susceptibility to atopic dermatitisand psoriasis vulgaris. J Dermatol Sci 2002; 30: 161-6.
20. Koppelman GH, Stine OC, Xu J, Howard TD, Zheng SL, KauffmanHF, et al. Genome-wide search for atopy susceptibility genesin Dutch families with asthma. J Allergy Clin Immunol 2002; 109:498-506.
21. Novak N, Kruse S, Potreck J, Maintz L, Jenneck C, Weidinger S, et al. Single nucleotide polymorphisms of the IL18 gene are associatedwith atopic eczema. J Allergy Clin Immunol 2005; 115: 828-33.
22. Sohn MH, Song JS, Kim KW, Kim ES, Kim KE, Lee JM. Associationof interleukin-10 gene promoter polymorphism in childrenwith atopic dermatitis. J Pediatr 2007; 150: 106-8.
23. Lacy K, Archer C, Wood N, Bidwell J. Association between acommon IL10 distal promoter haplotype and IgE production in individualswith atopic dermatitis. Int J Immunogenet 2009; 36: 213-6.
24. Schulz F, Marenholz I, Folster-Holst R, Chen C, Sternjak A, Baumgrass R, et al. A common haplotype of the IL-31 gene influencinggene expression is associated with nonatopic eczema. J AllergyClin Immunol 2007; 120: 1097-102.
25. Chan LS, Robinson N, Xu L. Expression of interleukin-4 in theepidermis of transgenic mice results in a pruritic inflammatory skindisease: An experimental animal model to study atopic dermatitis. JInvest Dermatol 2001; 117: 977-83.
26. Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenicexpression of interleukin-13 in the skin induces a pruriticdermatitis and skin remodeling. J Invest Dermatol 2009; 129(3):742-51.
27. Dillon SR, Sprecher C, Hammond A, Bilsborough J, Rosenfeld-Franklin M, Presnell SR, et al. Interleukin 31, a cytokine producedby activated T cells, induces dermatitis in mice. Nat Immunol2004; 5: 752-60.
28. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18regulates both Th1 and Th2 responses. Annu Rev Immunol 2001;19: 423-74.
29. Yamanaka K, Tanaka M, Tsutsui H, Kupper TS, Asahi K, OkamuraH, et al. Skin specific caspase-1-transgenic mice show cutaneousapoptosis and pre-endotoxin shock condition with a high serumlevel of IL-18. J Immunol 2000; 165: 997-1003.
30. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergicinflammation by producing TSLP. Nat Immunol 2002; 3: 673-80.
31. Yoo J, Omori M, Gyarmati D, Zhou B, Aye T, Brewer A, et al. Spontaneous atopic dermatitis in mice expressing an induciblethymic stromal lymphopoietin transgene specifically in the skin. JExp Med 2005; 202: 541-9.
32. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, et al. Cloning of a new cytokine that induces IFNgammaproduction by T cells. Nature 1995; 378(6552): 88-91.
33. Grimstad O, Sawanobori Y, Vestergaard C, Bilsborough J, OlsenUB, Grønhøj-Larsen C, et al. Antiinterleukin-31-antibodies amelioratescratching behavior in NC/Nga mice: A model of atopicdermatitis. Exp Dermatol 2009; 18: 35.
34. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahanTK, et al. IL-33, an interleukin-1-like cytokine that signals via theIL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005; 23: 479-90.
35. Kondo Y, Yoshimoto T, Yasuda K, Futatsugi-Yumikura S, KondoY, Yoshimoto T, et al. Administration of IL-33 induces airway hyperresponsivenessand goblet cell hyperplasia in the lungs in theabsence of adaptive immune system. Int Immunol 2008; 20: 791-800.
36. Kurowska-Stolarska M, Kewin P, Murphy G, Russo RC, StolarskiB, Garcia CC, et al. IL-33 induces antigen-specific IL-5+ T cellsand promotes allergic-induced airway inflammation independent ofIL-4. J Immunol 2008; 181: 4780-90.
37. Li L, Elliott JF, Mosmann TR. IL-10 inhibits cytokine roduction, vascular leakage, and swelling during T helper 1 cell-induced delayed-type hypersensitivity. J Immunol 1994; 153: 3967-78.
38. Stämpfli MR, Cwiartka M, Gajewska BU, Alvarez D, Ritz SA, Inman MD, et al. Interleukin-10 gene transfer to the airway regulatesallergic mucosal sensitization in mice. Am J Respir Cell MolBiol 1999; 21: 586-96.
39. Bellinghausen I, Brand U, Steinbrink K, Enk AH, Knop J, Saloga J. Inhibition of human allergic T cell responses by IL-10-treated dendriticcells: differences from hydrocortisone-treated dendritic cells. J Allergy Clin Immunol 2001; 108: 242-9.
40. Morris SC, Madden KB, Adamovicz JJ, Gause WC, Hubbard BR, Gately MK, et al. Effects of IL-12 on in vivo cytokine gene expressionand Ig isotype selection. J Immunol 1994; 152: 1047-56.
41. Williamson E, Garside P, Bradley JA, More IA, Mowat AM. NeutralizingIL-12 during induction of murine acute Graft-versus-hostdisease polarizes and cytokine profile toward a Th1-type alloimmuneresponse and confers long term protection from disease. JImmunol 1997; 159: 1208-15.
42. Noh G, Lee K. Blood eosinophils and serum IgE as predictors forprognosis of interferongamma therapy in atopic dermatitis. Allergy1998; 53: 1202-7.
43. Niwa Y. Elevated RANTES levels in plasma or skin and decreasedplasma IL-10 levels in subsets of patients with severe atopic dermatitis. Arch Dermatol.2000; 136:125-6.
44. Hamid Q, Naseer T, Minshall EM, Song YL, Boguniewicz M, Leung DY. In vivo expression of IL-12 and IL-13 in atopic dermatitis. J Allergy Clin Immunol 1996; 98:225-31.
45. Masuda K, Katoh N, Okuda F, Kishimoto S. Increased levels ofserum interleukin-16 in adult type atopic dermatitis. Acta DermVenereol 2003; 83: 249-53.
46. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possiblepathogenic role of Th17 cells for atopic dermatitis. J InvestDermatol 2008; 128: 2625-30.
47. Novak N, Bieber T. The role of dendritic cell subtypes in thepathophysiology of atopic dermatitis. J Am Acad Dermatol 2005:53; S171-6.
48. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: A new link between T cells and pruritus in atopic skininflammation. J Allergy Clin Immunol 2006; 117: 411-7.
49. Raap U, Wichmann K, Bruder M, Stander S, Wedi B, Kapp A, et al. Correlation of IL-31 serum levels with severity of atopicdermatitis. J Allergy Clin Immunol 2008; 122: 421-3.
50. Meyer N, Zimmermann M, Burgler S, Bassin C, Woehrl S, MoritzK, et al. IL-32 is expressed by human primary keratinocytes andmodulates keratinocyte apoptosis in atopic dermatitis. J AllergyClin Immunol 2010; 125: 858-65.
51. Sakashita M, Yoshimoto T, Hirota T, Harada M, Okubo K, OsawaY, et al. Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis. Clin Exp Allergy2008; 38: 1875-81.
52. Machura E, Mazur B, Kwiecień J, Karczewska K. Intracellularproduction of IL-2, IL-4, IFN-γ, and TNF-α by peripheral bloodCD3+ and CD4+ T cells in children with atopic dermatitis. Eur JPediatr 2007; 166: 789-95.
53. Vakirlis E, Lazaridou E, Tzellos TG, Gerou S, Chatzidimitriou D, Ioannides D. Investigation of cytokine levels and their associationwith SCORAD index in adults with acute atopic dermatitis. J EurAcad Dermatol Venereol 2011; 25: 409-16.
54. Novak N. New insights into the mechanism and management ofallergic diseases:Atopic dermatitis. Allergy 2009; 64: 265-75.
55. Klechevsky E, Morita R, Liu M, Cao Y, Coquery S, Thompson-Snipes L, et al. Functional specializations of human epidermalLangerhans cells and CD14+ dermal dendritic cells. Immunity2008; 29: 497-510.
56. Zaba LC, Fuentes-Duculan J, Steinman RM, Krueger JG, LowesMA. Normal human dermis contains distinct populations ofCD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages. J Clin Invest 2007; 117: 2517-25.
57. Morelli AE, Rubin JP, Erdos G, Tkacheva OA, Mathers AR, Zahorchak AF, et al. CD4+ T cell responses elicited by differentsubsets of human skin migratory dendritic cells. J Immunol 2005;175: 7905-15.
58. Mathers AR, Janelsins BM, Rubin JP, Tkacheva OA, Shufesky WJ, Watkins SC, et al. Differential capability of human cutaneous dendriticcell subsets to initiate Th17 responses. J Immunol 2009; 182:921-33.
59. Mehta DS, Wurster AL, Grusby. Biology of IL-21 and the IL-21. Immunol Rev 2004; 202: 84-95.
60. Spolski R, Leonard WJ. Interleukin-21: Basic biology and implicationsfor cancer and autoimmunity. Annu Rev Immunol 2008; 26:57-79.
61. Lancour M. Acute infections in atopic dermatitis. A clue for apathogenic role of a Th1/Th2 imbalance. Dermatol 1994;188: 255-7.
62. Tang M, Kemp A, Varigos G. IL-4 and interferon-gamma productionin children with atopic disease. Clin Exp Immunol 1993; 92:120-4.
63. Snapper CM, Paul WE. Interferon-[and B cell stimulatory factor-Ireciprocally regulate IgE isotype production. Science1987; 236:944-6.
64. Nakagawa S, Aiba S, Tagami H. Decreased frequency of interferon-producing CD4+ cells in the peripheral blood of patientswith atopic dermatitis. Exp Dermatol 1998; 7: 112-8.
65. Campbell DE, Fryga AS, Bol S, Kemp AS. Intracellular interferongamma(IFN-() production in normal children and children withatopic dermatitis. Clin Exp Immunol 1999; 115: 377-82.
66. D'Orazio J, Burke GW, Stein-Streilein J. Staphylococcal enterotoxinB activates purified NK cells to secrete IFN-gamma but requiresT lymphocytes to augment NK cytotoxicity. J Immunol1995; 154: 1014-23.
67. Jung T, Lack G, Schauer U, Uberück W, Renz H, Gelfand EW, et al. Decreased frequency of interferongamma-and interleukin-2-producing cells in patients with atopic diseases measured at thesingle cell level. J Allergy Clin Immunol 1995; 96: 515-27.
68. Tang ML, Kemp AS, Thorburn J, Hill DJ. Reduced interferongamma secretion in neonate and subsequent atopy. Lancet 1994;344: 983-5.
69. Warner JA, Miles EA, Jones AC, Quint DJ, Colwell BM, WarnerJO. Is deficiency of interferon gamma production by allergen triggeredcord blood cells a predictor of atopic eczema? Clin Exp Allergy1994; 24: 423-30.
70. Seder RA, Gazzinelli R, Sher A, Paul WE. Interleukin 12 actsdirectly on CD41 T cells to enhance priming for interferon gammaproduction and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci USA 1993; 90: 10188.
71. Wills-Karp M. IL-12/IL-13 axis in allergic asthma. J Allergy ClinImmunol 2001; 107: 9.
72. Trinchieri G. Interleukin-12: A cytokine at the interface of inflammationand immunity. Adv Immunol 1998; 70: 83-243.
73. Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, et al. Natural killer cell stimulatory factor (interleukin12 [IL-12]) induces T helper type 1(Th1)-specific immune responsesand inhibits the development of IL-4-producing Th cells. JExp Med 1993; 177: 1199.
74. Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, et al. IL-27, a heterodimeric cytokine composed of EBI3and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 2002; 16: 779-90.
75. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13: 715-25.
76. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, VignaliKM, et al. The inhibitory cytokine IL-35 contributes to regulatoryT-cell function. Nature 2007; 450: 566-9.
77. Niedbala W, Wei X Q, Cai B, Hueber AJ, Leung BP, McInnes IB, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cellsand suppression of Th17 cells. Eur J Immunol 2007; 37: 3021-9.
78. Yoshida H, Nakaya M, Miyazaki Y. Interleukin 27: A doubleedgedsword for offense and defense. J Leukoc Biol 2009; 86:1295-303.
79. Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, et al. WSX-1 and glycoprotein 130 constitute a signal-transducingreceptor for IL-27. J Immunol 2004; 172: 2225-31.
80. Yoshimura T, Takeda A, Hamano S, Miyazaki Y, Kinjyo I, IshibashiT, et al. Two-sided roles of IL-27: induction of Th1 differentiationon naive CD4+ T cells versus suppression of proinflammatorycytokine production including IL-23-induced IL-17 on activatedCD4+ T cells partially through STAT3-dependent mechanism. J Immunol 2003; 177: 5377-85.
81. Takeda A, Hamano S, Yamanaka A, Hanada T, Ishibashi T, MakTW, et al. Cutting edge: Role of IL-27/WSX-1 signaling for inductionof T-bet through activation of STAT1 during initial Th1 commitment. J Immunol 2003; 170: 4886-90.
82. Niebuhr M, Scharonow H, Gathmann M, Mamerow D, Werfel T. Staphylococcal exotoxins are strong inducers of IL-22: A potentialrole in atopic dermatitis. J Allergy Clin Immunol 2010; 126: 1176-83.
83. Magram J, Connaughton SE, Warrier RR, Carvajal D, Wu C, FerranteJ, et al. IL-12 deficient mice are defective in IFN-gammaproduction and type 0 cytokine responses. Immunity 1996; 4: 471.
84. Gillespie MT, Horwood NJ. IL-8 prespectives on the newest interleukin. Cytokine Growth Factor Rev 1998; 9: 109-16.
85. Herberth G, Heinrich J, Röder S, Figl A, Weiss M, Diez U, et al. Reduced IFN-gamma-and enhanced IL-4-producing CD4+ cordblood T cells are associated with a higher risk for atopic dermatitisduring the first 2 yr of life. Pediatr Allergy Immunol 2010; 21: 5-13.
86. Nakajima H, Takatsu K. Role of cytokines in allergic airway inflammation. Int Arch Allergy Immunol 2007; 142(4): 265-73.
87. Busse WW, Ring J, Huss-Marp J, Kahn JE. A review of treatmentwith mepolizumab, an anti-IL-5 mAb, in hypereosinophilic syndromesand asthma. J Allergy Clin Immunol 2010; 125: 803-13.
88. Chatila TA. Interleukin-4 receptor signaling pathways in asthmapathogenesis. Trends Mol Med 2004; 10: 493-9.
89. Fesenkova VI, Kurchenko AI, Castellani ML, Conti P, AnogeianakiA, Caraffa A, et al. Expression of Co-stimulatory moleculeson langerhans cells in lesional epidermis of human atopic dermatitis. Immunopharmacol Immunotoxicol 2007; 29: 487-98.
90. Andrews AL, Nordgren IK, Kirby I, Holloway JW, Holgate ST, Davies DE, et al. Cytoplasmic tail of IL-13Ralpha2 regulates IL-4signal transduction. Biochem Soc Trans 2009; 37: 873-6.
91. Brombacher F. The role of interleukin-13 in infectious diseases andallergy. Bioessays 2000; 22: 646-56.
92. Nieuwenhuizen N, Herbert DR, Brombacher F, Lopata AL. Differentialrequirements for interleukin (IL)-4 and IL-13 in protein contactdermatitis induced by Anisakis. Allergy 2009; 64: 1309-18.
93. Maneechotesuwan K, Yao X, Ito K, Jazrawi E, Usmani OS, AdcockIM, et al. Suppression of GATA-3 nuclear import and phosphorylation:A novel mechanism of corticosteroid action in allergicdisease. PLoS Med 2009; 6: e1000076.
94. Seder RA, Paul WE, Davis MM, Fazekas de St Groth B. The presenceof interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptortransgenic mice. J Exp Med 1992; 176: 1091-8.
95. Tachdjian R, Al Khatib S, Schwinglshackl A, Kim HS, Chen A, Blasioli J, et al. In vivo regulation of the allergic response by theIL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitorymotif. J Allergy Clin Immunol 2010; 125: 1128-36.
96. Chapoval S, Dasgupta P, Dorsey NJ, Keegan AD. Regulation of theT helper cell type 2 (Th2)/T regulatory cell (Treg) balance by IL-4and STAT6. J Leukoc Biol 2010; 87: 1011-8.
97. Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, et al. Interleukin 21 is a T helper (Th) cell 2 cytokinethat specifically inhibits the differentiation of naïve Th cells into interferongamma-producing Th1 cells. J Exp Med 2002; 196: 969-77.
98. Habib T, Nelson A, Kaushansky K. IL-21: A novel IL-2-familylymphokine that modulates B, T, and natural killer cell responses. J Allergy Clin Immunol 2003;112: 1033-45.
99. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, et al. Interleukin 21 and its receptor are involved in NKcell expansion and regulation of lymphocyte function. Nature 2000;408: 57-63.
100. Collins M, Whitters MJ, Young DA. IL-21 and IL-21 receptor: Anew cytokine pathway modulates innate and adaptive immunity. Immunol Res 2003; 28: 131-40.
101. Brandt K, Bulfone-Paus S, Jenckel A, Foster DC, Paus R, RuckertR. Interleukin-21 inhibits dendritic cell-mediated T cell activationand induction of contact hypersensitivity in vivo. J Invest Dermatol2003; 121: 1379-82.
102. Brandt K, Bulfone-Paus S, Foster DC, Ruckert R. Interleukin-21inhibits dendritic cell activation and maturation. Blood 2003; 102:4090-8.
103. Di Carlo E, Comes A, Orengo AM, Rosso O, Meazza R, MusianiP, et al. IL-21 induces tumor rejection by specific CTL and IFNgammadependent CXC chemokines in syngeneic mice. J Immunol2004; 172: 1540-7.
104. Suto A, Nakajima H, Hirose K, Suzuki K, Kagami S, Seto Y, et al. Interleukin 21 prevents antigen-induced IgE production by inhibitinggerm line C (epsilon) transcription of IL-4-stimulated B cells. Blood 2002; 100: 4565-73.
105. Yoshimoto T, Okada, K, Morishima N, Kamiya S, Owaki T, AsakawaM, et al. Induction of IgG2a class switching in B cells by IL-27. J Immunol 2004; 173: 2479-85.
106. Ozaki K, Spolski R, Feng CG, Qi C-F, Cheng J, Sher A, et al. Acritical role for IL-21 in regulating immunoglobulin production. Science 2002; 298: 1630-4.
107. Fujio K, Okamura T, Yamamoto K. The Family of IL-10-SecretingCD4(+) T Cells. Adv Immunol 2010; 105: 99-130.
108. Hobbs K, Negri J, KlinnertM, Rosenwasser LJ, Borish L. Interleukin-10 and transforming growth factor-beta promoter polymorphismsin allergies and asthma. Am J Respir Crit Care Med 1998;158: 1958-62.
109. Yang X, Wang S, Fan Y, Han X. IL-10 deficiency prevents IL-5overproduction and eosinophilic inflammation in a murine modelof asthma-like reaction. Eur J Immunol 2000; 30: 382-91.
110. Dunstan JA, Hale J, Breckler L, Lehmann H, Weston S, RichmondP, et al. Atopic dermatitis in young children is associated with impairedinterleukin-10 and interferon-g responses to allergens, vaccinesand colonizing skin and gut bacteria. Clin Exp Allergy 2005;35: 1309-17.
111. Laouini D, Alenius H, Bryce P, Oettgen H, Tsitsikov E, Raif S. IL-10 is critical for Th2 responses in a murine model of allergic dermatitisGeha J Clin Invest 2003;112: 1058-66.
112. Iwasaki A, Kelsall BL. Freshly isolated Peyer patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiationof T helper type 2 cells. J Exp Med 1999; 190: 229-39.
113. Jin H, Oyoshi MK, Le Y, Bianchi T, Koduru S, Mathias CB, et al. IL-21R is essential for epicutaneous sensitization and allergic skininflammation in humans and mice. Geha J Clin Invest 2009;119:47-60.
114. Mitchell EB, Chapman MD, Pope MF, Crow J, Jouhal SS, Plats-Mills TAE. Basophils in allergen induced patch test sites in atopicdermatitis. Lancet 1982; 1: 127-30.
115. Vickery BP. Skin barrier function in atopic dermatitis. Curr OpinPediatr 2007; 19: 89-93.
116. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermalbarrier protein filaggrin are a major predisposing factor for atopicdermatitis. Nat Genet 2006; 38: 441-6.
117. McGrath JA, Uitto J. The filaggrin story: Novel insights into skinbarrierfunction and disease. Trends Mol Med 2008; 14: 20-7.
118. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, DebenedettoA, et al. Cytokine modulation of atopic dermatitis filaggrinskin expression. J Allergy Clin Immunol 2007; 120: 150-5.
119. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, De-Benedetto A, Schneider L, Beck LA, Barnes KC, Leung DY. Cytokinemodulation of atopic dermatitis filaggrin skin expression. J AllergyClin Immunol 2009; 124(3 Suppl 2): R7-R12.
120. Barnes KC. An update on the genetics of atopic dermatitis:Scratching the surface in 2009. J Allergy Clin Immunol 2010; 125:16-29.
121. Seidenari S, Giusti G. Objective assessment of the skin of childrenaffected by atopic dermatitis: A study of pH, capacitance andTEWL in eczematous and clinically uninvolved skin. Acta DermVenereol 1995; 75: 429-33.
122. Werner Y, Lindberg M. Transepidermal water loss in dry and clinicallynormal skin in patients with atopic dermatitis. Acta DermVenereol 1985; 65: 102-5.
123. Goerdt S, Birk R, Dippel E, Orfanos CE. Beyond inflammation:Tolerance, immunotherapy and more. Eur J Dermatol 1999; 9: 507-13.
124. He R, Oyoshi MK, Jin H, Geha RS. Epicutaneous antigen exposureinduces a Th17 response that drives airway inflammation after inhalationchallenge. Proc Natl Acad Sci USA 2007; 104: 15817-22.
125. Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, GehaRS. Epicutaneous sensitization with protein antigen induces localizedallergic dermatitis and hyperresponsiveness to methacholineafter single exposure to aerosolized antigen in mice. J Clin Invest1998; 101: 1614-22.
126. Pandey A, Ozaki K, Baumann H, Levin SD, Puel A, Farr AG, et al. Cloning of a receptor subunit required for signaling by thymicstromal lymphopoietin. Nat Immunol 2000: 1; 59-64.
127. Ogawa T, Gunawan H, Ikeda S, Okumura K, Ogawa H. Cytokinemilieu modulates release of thymic stromal lymphopoietin fromhuman keratinocytes stimulated with double-stranded RNA. J AllergyClin Immunol 2009; 123: 179-86.
128. Herrick CA, Xu L, McKenzie AN, Tigelaar RE, Bottomly K. IL-13is necessary, not simply sufficient, for epicutaneously induced Th2responses to soluble protein antigen. J Immunol 2003; 170: 2488-95.
129. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P. TopicalVitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietinin mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci USA 2006; 103: 11736-41.
130. Li M, Hener P, Zhang Z, Ganti KP, Metzger D, Chambon P. Inductionof thymic stromal lymphopoietin expression in keratinocytes isnecessary for generating an atopic dermatitis upon application ofthe active vitamin D3 analogue MC903 on mouse skin. J InvestDermatol 2009; 129: 498-502.
131. Bilsborough J, Leung DY, Maurer M, Howell M, Boguniewicz M, Yao L, et al. IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J Allergy Clin Immunol 2006; 117: 418-25.
132. Breuer K, Kapp A, Werfel T. Bacterial infections and atopic dermatitis. Allergy 2001; 56: 1034-41.
133. Breuer K, Wittmann M, Bosche B, Kapp A, Werfel T. Severeatopic dermatitis is associated with sensitization to staphylococcalenterotoxin B (SEB). Allergy 2000; 55: 551-5.
134. Leung DYM, Harbeck R, Bina P, Reiser RF, Yang E, Norris DA, et al. Presence of IgE antibodies to staphylococcal exotoxins on theskin of patients with atopic dermatitis. J Clin Invest 1993; 92:1374-80.
135. Skov L, Olsen JV, Giorno L, Schlievert PM, Baadsgaard O, LeungDY. Application of staphylococcal enterotoxin B on normal andatopic skin induces up-regulation of T-cells by a superantigenmediatedmechanism. J Allergy Clin Immunol 2000; 105: 820-6.
136. McFadden JP, Noble WC, Camp RDR. Superantigenic exotoxinsecretingpotential of staphylococci isolated from atopic eczematousskin. Br J Dermatol 1993; 128: 631-2.
137. Breuer K, Wittmann M, Kempe K, Kapp A, Mai U, Dittrich-Breiholz O, et al. Alpha-toxin is produced by skin colonizingStaphylococcus aureus and induces a T helper type 1 response inatopic dermatitis. Clin Exp Allergy 2005; 35: 1088-95.
138. Wichmann K, Uter W, Weiss J, Breuer K, Heratizadeh A, Mai U, et al. Isolation of alpha-toxin-producing Staphylococcus aureusfrom the skin of highly sensitized adult patients with severe atopicdermatitis. Br J Dermatol 2009; 161: 300-5.
139. Sehra S, Yao Y, Howell MD, Nguyen ET, Kansas GS, Leung DY, et al. IL-4 regulates skin homeostasis and the predisposition towardallergic skin inflammation. J Immunol 2010; 184: 3186-90.
140. Ogg G. Role of T cells in the pathogenesis of atopic dermatitis. Clin Exp Allergy 2009; 39: 310-6.
141. Homey B, Steinhoff M, Ruzicka T, Leung DY. Cytokines andchemokines orchestrate atopic skin inflammation. J Allergy ClinImmunol 2006; 118: 178.
142. Matsumoto M, Sugiura H, Uehara M. Skin barrier function in patientswith completely healed atopic dermatitis. J Dermatol Sci2000; 23:178-82.
143. Morar N, Cookson WO, Harper JI, Moffatt MF. Filaggrin mutationsin children with severe atopic dermatitis. J Invest Dermatol2007; 127: 1667-72.
144. Nickoloff BJ, Naidu Y. Perturbation of epidermal barrier functioncorrelates with initiation of cytokine cascade in human skin. J AmAcad Dermatol 1994; 30: 535-46.
145. Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, GehaRS. Epicutaneous sensitization with protein antigen induces localizedallergic dermatitis and hyperresponsiveness to methacholineaftersingle exposure to aerosolized antigen in mice. J Clin Invest1998; 101: 1614-22.
146. Robert C, Kupper TS. Inflammatory skin diseases, T cells, andimmune surveillance. N Engl J Med 1999; 341: 1817-28.
147. Eigenmann PA. Mechanisms of food allergy. Pediatr Allergy Immunol2009; 20: 5-11.
148. Shub MD, Pang KY, Swann DA, Walker WA. Agerelated changesin chemical composition and physical properties of mucus glycoproteinsfrom rat small intestine. Biochem J 1983; 215: 405-11.
149. Hyman PE, Clarke DD, Everett SL, Sonne B, Stewart D, Harada T, et al. Gastric acid secretory function in pre-term infants. J Pediatr1985; 106: 467-71.
150. Untersmayr E, Jensen-Jarolim E. The effect of gastric digestion onfood allergy. Curr Opin Allergy Clin Immunol 2006; 6: 214-9.
151. Bresson JL, Pang KY, Walker WA. Microvillus membrane differentiation:Quantitative difference in cholera toxin binding to the intestinalsurface of newborn and adult rabbits. Pediatr Res 1984; 18:984-7.
152. Forbes EE, Groschwitz K, Abonia JP, Brandt EB, Cohen E, Blanchard C, et al. IL-9-and mast cell-mediated intestinal permeabilitypredisposes to oral antigen hypersensitivity. J Exp Med2008; 205: 897-913.
153. Rodríguez E, Baurecht H, Herberich E, Wagenpfeil S, Brown SJ, Cordell HJ, et al. Meta-analysis of filaggrin polymorphisms in eczemaand asthma: Robust risk factors in atopic disease. J AllergyClin Immunol 2009; 123: 1361-70.
154. Hanifin JM, Chan SC, Cheng JB, Tofte SJ, Henderson WR Jr, Kirby DS, et al. Type 4 phosphodiesterase inhibitors have clinicaland in vitro anti-inflammatory effects in atopic dermatitis. J InvestDermatol 1996; 107: 51-6.
155. Rudra, S., Gupta, N., Baregama, L.K., Agarwal, R., Khairnar, V.V., Ramaiah, M.R., Palle, V. P., Balachandran, S., Kondaskar, A., Salla, M., Ray, A., Dastidar, S.G., Vijaykrishnan, L. Pyrazolo (3, 4-B) pyridine derivatives as phosphodiesterase inhibitors. US2010292196 (2010) & NZ0579645A (2012) & EP2124944B1(2012).
156. Rudra, S., Gupta, N., Chandrakant, K.G., Jain, T., Voleti, S.R., Ray, A., Dastidar, S. G., Vijaykrishnan, L. Phosphodiestarase inhibitors. WO2010046791 (2010), EP2346867A1 (2011) &US20120004201 (2012).
157. Vercelli D. Genetic regulation of IgE responses: Achilles and thetortoise. J Allergy Clin Immunol 2005; 116: 60-4.
158. Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, WilliamsCM, Tsai M. Mast cells as "tunable" effector and immunoregulatorycells: recent advances. Annu Rev Immunol 2005;23: 749-86.
159. Marone G, Triggiani M, de PA. Mast cells and basophils: Friendsas well as foes in bronchial asthma? Trends Immunol 2005; 26: 25-31.
160. Novak N, Valenta R, Bohle B, Laffer S, Haberstok J, Kraft S, et al. FceRI engagement of Langerhans cell-like dendritic cells and inflammatorydendritic epidermal cell-like dendritic cells induceschemotactic signals and different T-cell phenotypes in vitro. J AllergyClin Immunol 2004; 113: 949-57.
161. llam JP, Klein E, Bieber T, Novak N. Transforming growth factorbeta1regulates the expression of the high-affinity receptor for IgEon CD34 stem cellderived CD1a dendritic cells in vitro. J InvestDermatol 2004; 123: 676-82.
162. Novak N, Tepel C, Koch S, Brix K, Bieber T, Kraft S. Evidence fora differential expression of the FceRIgamma chain in dendriticcells of atopic and nonatopic donors. J Clin Invest 2003; 111: 1047-56.
163. Novak N, Kraft S, Haberstok J, Geiger E, Allam P, Bieber T. Areducing microenvironment leads to the generation of FceRIhighinflammatory dendritic epidermal cells (IDEC). J Invest Dermatol2002;119: 842-9.
164. Chung F. Anti-inflammatory cytokines in asthma and allergy:Interleukin-10, interleukin-12, interferon-g. Med Inflamm 2001;10: 51-9.
165. Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY. IgEversus IgG4 production can be differentially regulated by IL-10. JImmunol 1998; 160: 3555-61.
166. Thompson-Snipes LA, Dhar V, Bond MW, Mosmann TR, MooreKW, Rennick DM. Interleukin 10: A novel stimulatory factor formast cells and their progenitors. J Exp Med 1991; 173: 507-10.
167. Lacraz S, Nicod LP, Chicheportiche R, Welgus HG, Dayer JM. IL-10 inhibits metalloproteinase and stimulates TIMP-1 production inhuman mononuclear phagocytes. J Clin Invest 1995; 96: 2304-10.
168. Novak N, Allam JP, Hagemann T, Jenneck C, Laffer S, Valenta R, et al. Characterization of FceRI-bearing CD123 blood dendritic cellantigen-2 plasmacytoid dendritic cells in atopic dermatitis. J AllergyClin Immunol 2004; 114: 364-70.
169. Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M, et al. Plasmacytoid dendritic cells: A new cutaneousdendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002;119: 1096-2.
170. Fujita H, Nogralesa KE, Kikuchia T, Gonzalezb J, Caruccic JA, Kruegera JG. Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. PNAS 2009;106: 21795-800.
171. Johnson-Huang LM, McNutt NS, Krueger JG, Lowes MA. Cytokine-producing dendritic cells in the pathogenesis of inflammatoryskin diseases. J Clin Immunol 2009; 29: 247-56.
172. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Whynot J, Novitskaya I, Cardinale I, et al. Major differences in inflammatorydendritic cells and their products distinguish atopic dermatitis frompsoriasis. J Allergy Clin Immunol 2009; 119: 1210-7.
173. Allakhverdi Z, Comeau MR, Jessup HK, Yoon BR, Brewer A, Chartier S, et al. Thymic stromal lymphopoietin is released by humanepithelial cells in response to microbes, trauma, or inflammationand potently activates mast cells. J Exp Med 2007: 204; 253-8.
174. Bogiatzi SI, Fernandez I, Bichet JC, Marloie-Provost MA, Volpe E, Sastre X, et al. Cutting Edge: Proinflammatory and Th2 cytokinessynergize to induce thymic stromal lymphopoietin production byhuman skin keratinocytes. J Immunol 2007; 178: 3373-7.
175. He R, Oyoshi MK, Garibyan L, Kumar L, Ziegler SF, Geha RS. TSLP acts on infiltrating effector T cells to drive allergic skin inflammation. Proc Natl Acad Sci USA 2008; 105: 11875-80.
176. Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T, et al. T cell-mediated Fas-induced keratinocyte apoptosisplays a key pathogenetic role in eczematous dermatitis. J Clin Invest2000;106: 25-35.
177. Trautmann A, Akdis M, Schmid-Grendelmeier P, Disch R, BrockerEB, Blaser K, Akdis CA. Targeting keratinocyte apoptosis in thetreatment of atopic dermatitis and allergic contact dermatitis. J AllergyClin Immunol 2001;108: 839-46.
178. Dinarello CA. Interleukin-18. Methods 1999; 19: 121-32.
179. Bieber T. Atopic dermatitis. N Engl J Med 2008; 358: 1483-94.
180. Leung DY, Bhan AK, Schneeberger EE, Geha RS. Characterizationof the mononuclear cell infiltrate in atopic dermatitis using monoclonalantibodies. J Allergy Clin Immunol 1983; 71: 47-56.
181. Leung DY, Schneeberger EE, Siraganian RP, Geha RS, Bhan AK. The presence of IgE on macrophages and dendritic cells infiltratinginto the skin lesion of atopic dermatitis. Clin Immunol Immunopathol1987; 42: 328-37.
182. Toda M, Leung DY, Molet S, Boguniewicz M, Taha R, ChristodoulopoulosP, et al. Polarized in vivo expression of IL-11 and IL17 between acute and chronic skin lesions. J Allergy Clin Immunol2003; 111: 875-81.
183. Eyerich K, Pennino D, Scarponi C, Foerster S, Nasorri F, BehrendtH, et al. IL-17 in atopic eczema: Linking allergen-specific adaptiveand microbial-triggered innate immune response. J Allergy ClinImmunol 2009; 123: 59-66.
184. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al. Interleukin (IL)-22 and IL-17 arecoexpressed by Th17 cells and cooperatively enhance expression ofantimicrobial peptides. J Exp Med 2006; 203: 2271-9.
185. Guttman-Yassky E, Lowes M A, Fuentes-Duculan J, Zaba LC, Cardinale I, Nograles KE, et al. Low expression of the IL-23/Th17pathway in atopic dermatitis compared to psoriasis. J Immunol2008; 181: 7420-7.
186. Liu YJ. Thymic stromal lymphopoietin and OX40 ligand pathwayin the initiation of dendritic cell-mediated allergic inflammation. JAllergy Clin Immunol 2007; 120: 238-44.
187. McGeachy MJ, Cua DJ. Th17 cell differentiation: The long andwinding road. Immunity 2008; 28: 445-53.
188. Sehra S, Bruns HA, Ahyi AN, Nguyen ET, Schmidt NW, MichelsEG, et al. IL-4 is a critical determinant in the generation of allergicinflammation initiated by a constitutively active STAT6. J Immunol2008; 180: 3551-9.
189. Wurster AL, Withers DJ, Uchida T, White MF, Grusby MJ. STAT6 and IRS-2 cooperate in interleukin 4 (IL-4)-induced proliferationand differentiation but are dispensable for IL-4-dependentrescue from apoptosis. Mol Cell Biol 2002; 22: 117-26.
190. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, DamschroderMM, et al. MEDI-563, a humanized anti-IL-5 receptor alphamAb with enhanced antibody-dependent cell-mediated cytotoxicityfunction. J Allergy Clin Immunol 2010; 125: 1344-53.
191. Kagami S, Saeki H, Komine M, Kakinuma T, Tsunemi Y, NakamuraK, et al. Interleukin-4 and interleukin-13 enhance CCL26production in a human keratinocyte cell line, HaCaT cells. ClinExp Immunol 2005; 141: 459-66.
192. Bae SJ, Lee JB, Shimizu K, Kuwazuka Y. Increase effect of transforminggrowth factor on eotaxin production by normal cultureddermal fibroblasts stimulated with interleukin-4: Inhibitory effectof suplatast tosilate on eotaxin production. Immunol Invest 2010;39: 93-102.
193. Nishi N, Yamamoto S, Ou W, Muro E, Inada Y, Hamasaki Y. Enhanced CCL26 production by IL-4 through IFN-gamma-inducedupregulation of type 1 IL-4 receptor in keratinocytes. BiochemBiophys Res Commun 2008; 376: 234-40.
194. Kinoshita H, Takai T, Le TA, Kamijo S, Wang XL, Ushio H, et al. Cytokine milieu modulates release of thymic stromal lymphopoietinfrom human keratinocytes stimulated with doublestrandedRNA. J Allergy Clin Immunol 2009; 123: 179-86.
195. Purwar R, Kraus M, Werfel T, Wittmann M. Modulation of keratinocyte-derived MMP-9 by IL-13: A possible role for the pathogenesisof epidermal inflammation. J Invest Dermatol 2008; 128:59-66.
196. Purwar R, Werfel T, Wittmann M. IL-13-stimulated human keratinocytespreferentially attract CD4+CCR4+ T cells: Possible role inatopic dermatitis. J Invest Dermatol 2006; 126: 1043-51.
197. Abernathy-Carver KJ, Sampson HA, Picker LJ, Leung DY. Milkinducedeczema is associated with the expansion of T cells expressingcutaneous lymphocyte antigen. J Clin Invest 1995; 95: 913-8.
198. Reekers R, Beyer K, Niggemann B, Wahn U, Freihorst J, Kapp A, et al. The role of circulating food antigen-specific lymphocytes infood allergic children with atopic dermatitis. Br J Dermatol1996;135: 935-41.
199. van Reijsen FC, Bruijnzeel-Koomen CA, Kalthoff FS, Maggi E, Romagnani S, Westland JK, et al. Skinderived aeroallergenspecificT-cell clones of Th2 phenotype in patients with atopicdermatitis. J Allergy Clin Immunol 1992; 90: 184-93.
200. van Reijsen FC, Felius A, Wauters EA, Bruijnzeel-Koomen CA, Koppelman SJ. T-cell reactivity for a peanut-derived epitope in theskin of a young infant with atopic dermatitis. J Allergy Clin Immunol1998;101: 207-9.
201. Suomalainen H, Soppi E, Isolauri E. Evidence for eosinophil activationin cow's milk allergy. Pediatr Allergy Immunol 1994; 5: 27-31.
202. Magnarin M, Knowles A, Ventura A, Vita F, Fanti L, Zabucchi G. A role for eosinophils in the pathogenesis of skin lesions in patientswith food sensitive atopic dermatitis. J Allergy Clin Immunol 1995;96: 200-8.
203. Noh G, Jin H, Lee J, Noh J, Lee WM, Lee S. Eosinophilia as apredictor of food allergy in atopic dermatitis. Allergy Asthma Proc2010; 31:e18-e24.
204. Lake AM, Whitington PF, Hamilton SR. Dietary protein-inducedcolitis in breast-fed infants. J Pediatr 1982; 101: 906-10.
205. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults: Asystematic review and consensus recommendations for diagnosisand treatment. Gastroenterology 2007; 133: 1342-63.
206. Mishra A, Rothenberg ME. Intratracheal IL-13 induces eosinophilicesophagitis by an IL-5, eotaxin-1, and STAT6-dependentmechanism. Gastroenterology 2003; 125: 1419-27.
207. Akei HS, Mishra A, Blanchard C, Rothenberg ME. Epicutaneousantigen exposure primes for experimental eosinophilic esophagitisin mice. Gastroenterology 2005; 129: 985-94.
208. Beyer K, Castro R, Feidel C, Sampson HA. Milk-induced urticariais associated with the expansion of T cells expressing cutaneouslymphocyte antigen. J Allergy Clin Immunol 2002; 109: 688-93.
209. Werfel T. The role of leukocytes, keratinocytes, and allergenspecificIgE in the development of atopic dermatitis. J Invest Dermatol2009; 129: 1878-91.
210. Lipozencić J, Pastar Z, Kulisić SM, Pavić I. Immunologic aspectsof atopic dermatitis. Acta Dermatovenerol Croat 2009; 17: 226-34.
211. Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokinegene expression in acute versus chronic atopic dermatitis. J ClinInvest 1994; 94: 870-6.
212. Jin H, Kumar L, Mathias C, Zurakowski D, Oettgen HC, Gorelik L, Geha RS. Toll-like receptor 2 is important for the Th1 response tocutaneous sensitization. J Allergy Clin Immunol 2009; 123: 875-82.
213. Grewe M, Gyufko K, Schopf E, Krutman J. Lesional expression ofinterferon-gamma in atopic eczema. Lancet 1994; 343: 25-6.
214. Trinchieri G. Interleukin-12: A proinflammatory cytokine withimmunoregulatory functions that bridge innate resistance and antigenspecificadaptive immunity. Annu Rev Immunol 1995; 13: 251-76.
215. Barbulescu K, Becker C, Schlaak JF, Schmitt E, Meyer zum BüschenfeldeKH, Neurath MF. IL-12 and IL-18 differentially regulatethe transcriptional activity of the human IFN-gamma promoterin primary CD4+T lymphocytes. J Immunol 1998; 160: 3642-7.
216. Yawalkar N, Karlen S, Egli F, Brand CU, Graber HU, Pichler WJ, et al. Down-regulation of IL-12 by topical corticosteroids inchronic atopic dermatitis. J Allergy Clin Immunol 2000; 106: 941-7.
217. Tazawa T, Sugiura H, Sugiura Y, Uehara M. Relative importanceof IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch DermatolRes 2004; 295(11): 459-64.
218. Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S, et al. Th22 cells represent a distinct human T cell subset involvedin epidermal immunity and remodelling. J Clin Invest 2009; 119:3573-85.
219. Matsumoto, K., Yagami, S., Nimura, K., Saito, H. Marker for judgingpredisposing factor of atopy, marker for judging predisposingfactor of allergic skin disease and method for using the same. JP2010207200 (2010).
220. Cruikshank WW, Kornfeld H, Center DM. Interleukin-16. J LeukocBiol 2000; 67: 757-66.
221. Kaser A, Dunzendorfer S, Offner FA, Ludwiczek O, Enrich B, Koch RO, et al. B lymphocyte-derived IL-16 attracts dendritic cellsand Th cells. J Immunol 2000; 165: 2474-80.
222. Liu Y, Cruikshank W, O'Loughlin T, O'Reilly P, Center DM, Kornfeld H. Identification of a CD4 domain required for IL-16binding and lymphocyte activation. J Biol Chem 1999; 274: 23387-95.
223. Mathy NL, Scheuer W, Lanzendorfer M, Honold K, Ambrosius D, Norley S, et al. Interleukin-16 stimulates the expression and productionof pro-inflammatory cytokines by human monocytes. Immunology2000; 100: 63-9.
224. Parada NA, Center DM, Kornfeld H, Rodriguez WL, Cook J, Vallen M, et al. Synergistic activation of CD4+ T cells by IL-16and IL-2. J Immunol 1998; 60: 2115-120.
225. Laberge S, Cruikshank WW, Beer DJ, Center DM. Secretion of IL-16 (lymphocyte chemoattractant factor) from serotonin-stimulatedCD8+ T cells in vitro. J Immunol 1996;156:310-5.
226. Laberge S, Cruikshank WW, Kornfeld H, Center DM. Histamineinducedsecretion of lymphocyte chemoattractant factor fromCD8+ T cells is independent of transcription and translation: evidencefor constitutive protein synthesis and storage. J Immunol1995; 55:2902-10.
227. Wu D, Zhang Y, Parada N, Kornfeld H, Nicoll J, Center DM, et al. Processing and release of IL-16 from CD4+ but not CD8+ T cellsis activation dependent. J Immunol 1999; 162:1287-93.
228. Laberge S, Ghaffar O, Boguniewicz M, Center DM, Leung DY, Hamid Q. Association of increased CD4+ T-cell infiltration withincreased IL-16 gene expression in atopic dermatitis. J Allergy ClinImmunol 1998; 102: 615-50.
229. Fischer A, Hipler UC, Bauer A, Fluhr JW, Tsankov N, FischerTW, et al. Significance of interleukin-16, macrophage-derivedchemokine, eosinophil cationic protein and soluble E-selectin in reflectingdisease activity of atopic dermatitis-from laboratory parametersto clinical scores. Br J Dermatol 2006;154: 1112-7.
230. Lim KG, Wan HC, Bozza PT, Resnik MB, Wong DTW, CruikshankWW, et al. Human eosinophils elaborate the lymphocytechemoattractants: IL-16 (lymphocyte chemoattractant factor) andRANTES. J Immunol 1996; 156: 3566-70.
231. Rumsaeng V, Cruikshank WW, Foster B, Prussin C, KirshenbaumAS, Davis TA, et al. Human mast cells produce the CD4+ T lymphocytechemoattractant factor, IL-16. J Immunol 1997; 159: 2904-10.
232. Reich K, Heine A, Hugo S, Blaschke V, Middel P, Kaser A, et al. Engagement of the FceRI stimulates the production of IL-16 inLangerhans cell-like dendritic cells. J Immunol 2001; 167: 6321-9.
233. Laberge S, Pinsonneault S, Ernst P, Olivenstein R, Ghaffar O, Center DM, et al. Phenotype of IL-16-producing cells in bronchialmucosa: Evidence for the human eosinophil and mast cell as cellularsources of IL-16 in asthma. Int Arch Allergy Immunol 1999;119: 120-5.
234. Yoshimoto T, Wang CR, Yoneto T, Matsuzawa A, CruikshankWW, Nariuchi H. Role of IL-16 in delayedtype hypersensitivity reaction. Blood 2000; 95: 2869-74.
235. Bandeira-Melo C, Sugiyama K, Woods LJ, Phoofolo M, CenterDM, Cruikshank WW, et al. IL-16 promotes leukotriene C4 andIL-4 release from human eosinophils via CD4-and autocrineCCR3-chemokine-mediated signaling. J Immunol 2002; 168: 4756-63.
236. Bratton DL, Hamid Q, Boguniewicz M, Doherty DE, Kailey JM, Leung DY. Granulocyte macrophage colonystimulating factor contributesto enhanced monocytes survival in chronic atopic dermatitis. J Clin Invest 1995; 95: 211-8.
237. Katoh N, Kraft S, Weßendorf JHM, Bieber T. The high affinity IgEreceptor (FceRI) blocks apoptosis in normal human monocytes. JClin Invest 2000; 105: 183-90.
238. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, et al. Transforming growth factor-beta inducesdevelopment of the T(H)17 lineage. Nature 2006; 441: 231-4.
239. Bettelli E, Carrier Y, GaoW, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogeniceffector TH17 and regulatory T cells. Nature 2006; 441: 235-8.
240. Diveu C, McGeachy MJ, Boniface K, Stumhofer JS, Sathe M, Joyce-Shaikh B, et al. IL-27 blocks RORc expression to inhibitlineage commitment of Th17 cells. J Immunol 2009; 182: 5748-56.
241. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1 and 6 but not transforming growth factor-eeare essentialfor the differentiation of interleukin 17-producing human Thelper cells. Nat Immunol 2007; 8: 942-9.
242. Schmidt-Weber CB, Akdis M, Akdis CA. TH17 cells in the bigpicture of immunology. J Allergy Clin Immunol 2007; 120: 247-54.
243. Chow JYS, Wong CK, Cheung PFY, Lam CWK. Intracellularsignaling mechanisms regulating the activation of human eosinophilsby the novel Th2 cytokine IL-33: Implications for allergic inflammation. Cell Mol Immunol 2010; 7: 26-34.
244. Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H. Identificationof a human helper T cell population that has abundant productionof interleukin 22 and is distinct from Th-17, Th1 and Th2 cells. NatImmunol 2009; 10: 864-71.
245. Nograles CE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, et al. IL-22-producing T22 T cells account for upregulatedIL-22 in atopic dermatitis despite reduced IL-17-producingTh17 T cells. J Allergy Clin Immunol 2009; 123:1244-52.
246. Ouyang W, Kolls JK, Zheng Y. The biological functions of Thelper 17 cell effector cytokines in inflammation. Immunity 2008;28: 454-67.
247. Spolski R, Leonard WJ. Cytokine mediators of Th17 function. EurJ Immunol 2009; 39: 658-61.
248. Zenewicz LA, Flavell RA. IL-22 and inflammation: Leukin'through a glass onion. Eur J Immunol 2008; 38: 3265-8.
249. Gurney AL. IL-22, a Th1 cytokine that targets the pancreas andselect other peripheral tissues. Int Immunopharmacol 2004; 4: 669-77.
250. Wolk K, Kunz S, Asadullah K, Sabat R. Immune cells as sourcesand targets of the IL-10 family members? J Immunol 2002; 168:5397-402.
251. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-AndersonJ, Wu J, et al. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007; 445:648-51.
252. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JKM, et al. A human natural killer cell subset provides an innate sourceof IL-22 for mucosal immunity. Nature 2009; 457: 722-5.
253. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, et al. Interleukin-22 mediates early host defense against attaching and effacingbacterial pathogens. Nat Med 2008; 14: 282-9.
254. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Productionof interleukin 22 but not interleukin 17 by a subset of humanskin-homing memory T cells. Nat Immunol 2009; 10: 857-63.
255. Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C. Expressionand regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res 2006; 16: 902-7.
256. Wolk K, Sabat R. Interleukin-22: A novel T and NK cell-derivedcytokine that regulates the biology of tissue cells. Cytokine GrowthFactor Rev 2006;17:367-80.
257. Lopez-Bravo M, Ardavin C. In vivo induction of immune responsesto pathogens by conventional dendritic cells. Immunity 2008; 29:343-51.
258. Volpe E, Touzot M, Servant N, Marloie-Provost MA, Hupé P, Barillot E, et al. Multiparametric analysis of cytokine-driven humanTh17 differentiation reveals a differential regulation of IL-17and IL-22 production. Blood 2009; 114: 3610-14.
259. Nograles KE, Zaba LC, Guttman-Yassky E, Fuentes-Duculan J, Suárez-Fariñas M, Cardinale I, et al. Th17 cytokines interleukin(IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol 2008; 159: 1092-102.
260. Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, MorelF. IL-22 inhibits epidermal differentiation and induces proinflammatorygene expression and migration of human keratinocytes. JImmuno 2005; 174: 3695-702.
261. Sa SM, Valdez PA, Wu J, Jung K, Zhong F, Hall L, et al. Theeffects of IL-20 subfamily cytokines on reconstituted human epidermissuggest potential roles in cutaneous innate defense andpathogenic adaptive immunity in psoriasis. J Immunol 2007; 178:2229-40.
262. Cheung PFY, Wong CK, Ho AMY, Hu S, Chen DP, Lam CWK. Activation of human eosinophils and epidermal keratinocytes byTh2 cytokine IL-31: Implication for the immunopathogenesis ofatopic dermatitis. Int Immunol 2010; 22: 453-67.
263. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-NewenG, Schaper F. Principles of interleukin (IL)-6-type cytokine signallingand its regulation. Biochem J 2003; 374: 1-20.
264. Raap U, Weißmantel S, Gehring M, Eisenberg AM, Kapp A, Fölster-Holst R. IL-31 significantly correlates with disease activity andTh2 cytokine levels in children with atopic dermatitis. Pediatr AllergyImmunol 2012; 23(3):285-8.
265. Bilsborough J, Leung DY, Maurer M, Howell M, Boguniewicz M, Yao L, et al. IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J Allergy Clin Immunol 2006; 117(2): 418-25.
266. Takaoka A, Arai I, Sugimoto M, Yamaguchi A, Tanaka M, NakaikeS. Expression of IL-31 gene transcripts in NC/Nga mice withatopic dermatitis. Eur J Pharmacol 2005; 516: 180.
267. Dreuw A, Radtke S, Pflanz S, Lippok BE, Heinrich PC. HermannsHM. Characterization of the signaling capacities of the novelgp130-like cytokine receptor. J Biol Chem 2004; 279: 36112.
268. Diveu C, Lak-Hal AH, Froger J, Ravon E, Grimaud L, Barbier F, et al. Predominant expression of the long isoform of GP130-like(GPL) receptor is required for interleukin-31 signaling. Eur CytokineNetw 2004; 15: 291-302.
269. Jawa RS, Chattopadhyay S, Tracy E, Wang Y, Huntoon K, DaytonMT, et al. Regulated expression of the IL-31 receptor in bronchialand alveolar epithelial cells, pulmonary fibroblasts, and pulmonarymacrophages. J Interferon Cytokine Res 2008; 28: 207.
270. Chattopadhyay S, Tracy E, Liang P, Robledo O, Rose-John S, Baumann H. Interleukin-31 and oncostatin-M mediate distinct signalingreactions and response patterns in lung epithelial cells. JBiol Chem 2007; 282: 3014-26.
271. Takaoka A, Arai L, Sugimoto M, Honma Y, Futaki N, Nakamura A, et al. Involvement of IL-31 on scratching behavior in NC/Nga micewith atopic-like dermatitis. Exp Dermatol 2006; 15: 161-7.
272. Choi, W. S., Song, H., Kim, J. W., Park, K. L., Sohn, K. H., Lee, J.K., Ju, J. H., Kim, J. H., Kim, I. Y., Lim, C. H., Hong, S. K. Atopic dermatitis model animal and method for constructing thesame. KR20100098476 (2010).
273. Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C, et al. Enhanced expression levels of IL-31 correlate with IL-4 and IL-13in atopic and allergic contact dermatitis. J Allergy Clin Immunol2006; 118: 930-7.
274. Miraglia del Giudice M, Decimo F, Leonardi S, Maioello N, Amelio R, Capasso A, et al. Immune dysregulation in atopic dermatitis. Allergy Asthma Proc 2006; 27: 451-5.
275. Simon D, Braathen LR, Simon HU. Eosinophils and atopic dermatitis. Allergy 2004; 59: 561-70.
276. Bruijnzeel PL, Kuijper PH, Kapp A, Warringa RA, Betz S, Bruijnzeel-Koomen CA. The involvement of eosinophils in thepatch test reaction to aeroallergens in atopic dermatitis: Its relevancefor the pathogenesis of atopic dermatitis. Clin Exp Allergy1993; 23: 97-109.
277. Maeda K, Yamamoto K, Tanaka Y, Anan S. Yoshida H. The relationshipbetween eosinophils, OKT6-positive cells and house dustmite (HDM) antigens in naturally occurring lesions of atopic dermatitis. J Dermatol Sci 1992; 3:151-6.
278. Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, et al. Development of atopic dermatitis-like skin lesion with IgEhyperproduction in NC/Nga mice. Int Immunol 1997; 9: 461-6.
279. Kiehl P, Falkenberg K, Vogelbruch M, Kapp A. Tissue eosinophiliain acute and chronic atopic dermatitis: A morphometric approachusing quantitative image analysis of immunostaining. Br JDermatol 2001; 145: 720-9.
280. Uehara M, Izukura R, Sawai T. Blood eosinophilia in atopic dermatitis. Clin Exp Dermatol 1990; 15: 264.
281. Kagi MK, Joller-Jemelka H, Wuthrich B. Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptorwith the clinical activity of atopic dermatitis. Dermatology 1992;185: 88-92.
282. Kondo S, Yazawa H, Jimbow K. Reduction of serum interleukin-5levels reflect clinical improvement in patients with atopic dermatitis. J Dermatol 2001: 28; 237-43.
283. Taha RA, Minshall EM, Leung DY, Boguniewicz M, Luster A, Muro S, et al. Evidence for increased expression of eotaxin andmonocytes chemotactic protein-4 in atopic dermatitis. J AllergyClin Immunol 2000; 105; 1002-7.
284. Yawalkar N, Uguccioni M, Scharer J, Braunwalder J, Karlen S, Dewald B, et al. Enhanced expression of eotaxin and CCR3 inatopic dermatitis. J Invest Dermatol 1999; 113: 43-8.
285. Takatsu K, Kouro T, Nagai Y. Interleukin 5 in the link between theinnate and acquired immune response. Adv Immunol 2009; 101:191-236.
286. Yamada T, Sun Q, Zeibecoglou K, Bungre J, North J, Kay AB, et al. S. IL-3, IL-5, granulocyte-macrophage colony-stimulatingfactor receptor alpha-subunit, and common beta-subunit expressionby peripheral leukocytes and blood dendritic cells. J Allergy ClinImmunol 1998; 101: 677-82.
287. Simon D, Braathen LR, Simon HU. Eosinophils and atopic dermatitis. Allergy 2004; 59: 561-70.
288. Liu LY, Sedgwick JB, Bates ME, Vrtis RF, Gern JE, Kita H, JarjourNN, et al. Decreased expression of membrane IL-5 receptoralpha on human eosinophils: I. Loss of membrane IL-5 receptor alphaon airway eosinophils and increased soluble IL-5 receptor alphain the airway after allergen challenge. J Immunol 2002;169(11): 6452-8.
289. Semic-Jusufagic A, Gevaert P, Bachert C, Murray C, Simpson A, Custovic A. Increased serum-soluble interleukin-5 receptor alphalevel precedes the development of eczema in children. Pediatr AllergyImmunol 2010; 21: 1052-8.
290. Kagami S, Nakajima H, Kumano K, Suzuki K, Suto A, Imada K, et al. Both stat5a and stat5b are required for antigen-induced eosinophiland T-cell recruitment into the tissue. Blood 2000; 95: 1370-7.
291. Walsh GM, Hartnell A, Wardlaw AJ, Kurihara K, Sanderson CJ, Kay AB. IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependentmanner. Immunology 1990; 71: 258-65.
292. Park YM, Bochner BS. Eosinophil survival and apoptosis in healthand disease. Allergy Asthma Immunol Res 2010; 2: 87-101.
293. Kouro T, Takatsu K. IL-5-and eosinophil-mediated inflammation:from discovery to therapy. Int Immunol 2009; 21: 1303-9.
294. Yaoa W, Change J, Sehraa S, Traversb JB, Change CH, Teppera RS, et al. Altered cytokine production by dendritic cells from infantswith atopic dermatitis. Clin Immunol 2010; 137: 406-14.
295. Taniuchi S, Chihara J, Kojima T, Yamamoto A, Sasai M, KobayashiY. Serum eosinophil derived neurotoxin may reflect morestrongly disease severity in childhood atopic dermatitis than eosinophilcationic protein. J Dermatol Sci 2001; 26: 79-82.
296. Barksby HE, Lea SR, Preshaw PM, Taylor JJ. The expanding familyof interleukin-1 cytokines and their role in destructive inflammatorydisorders. Clin Exp Immunol 2007; 149: 217-25.
297. Allakhverdi Z, Smith DE, Comeau MR, Delespesse G. Cuttingedge: The ST2 ligand IL-33 potently activates and drives maturationof human mast cells. J Immunol 2007; 179: 2051-4.
298. Iikura M, Suto H, Kajiwara N, Oboki K, Ohno T, Okayama Y, et al. IL-33 can promote survival, adhesion and cytokine productionin human mast cells. Lab Invest 2007; 87: 971-8.
299. Pecaric-Petkovic T, Didichenko SA, Kaempfer S, Spiegl N, DahindenCA. Human basophils and eosinophils are the direct target leukocytesof the novel IL-1 family member IL-33. Blood 2009; 113:1526-34.
300. Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, LiewFY. IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol2007; 37: 2779-86.
301. Smithgall MD, Comeau MR, Yoon BR, Kaufman D, Armitage R, Smith DE. IL-33 amplifies both Th1-and Th2-type responsesthrough its activity on human basophils, allergen-reactive Th2cells, iNKT and NK cells. Int Immunol 2008; 20: 1019-30.
302. Wong CK, Zhang J, Ip WK, Lam CW. Intracellular signal transductionin eosinophils and its clinical significance. ImmunopharmacolImmunotoxicol 2002; 24:165-86.
303. Whitcomb EA, Dinarello CA, Pincus SH. Differential effects ofinterleukin-1 alpha and interleukin-1 beta on human peripheralblood eosinophils. Blood 1989; 73: 1904-8.
304. Wang W, Tanaka T, Okamura H, Sugita M, Higa S, Kishimoto T, et al. Interleukin-18 enhances the production of interleukin-8 byeosinophils. Eur J Immunol 2001; 31: 1010-6.
305. Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families ofcytokines. Immunol Rev 2008; 223: 20-38.
306. Vignola AM, Chanez P, Chiappara G, Siena L, Merendino A, ReinaC, et al. Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients withasthma and chronic bronchitis. J Allergy Clin Immunol 1999; 103:563-73.
307. Kankaanranta H, Lindsay MA, Giembycz MA, Zhang X, MoilanenE, Barnes PJ. Delayed eosinophil apoptosis in asthma. J AllergyClin Immunol 2000; 106:77-83.
308. Pastore S, Mascia F, Girolomoni G. The contribution of keratinocytesto the pathogenesis of atopic dermatitis. Eur J Dermatol 2006;16: 125-31.
309. Pastore S, FanalesBelasio E, Albanesi C, Chinni LM, Giannetti A, Girolomoni G. Granulocyte macrophage colony-stimulating factoris overproduced by keratinocytes in atopic dermatitis-Implicationsfor sustained dendritic cell activation in the skin. J Clin Invest1997: 99; 3009-17.
310. Wolk K, Witte E, Wallace E, Docke W-D, Kunz S, et al. IL-22regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: A potentialrole in psoriasis. Eur J Immunol 2006; 36: 1309-23.
311. Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, et al. IL-22is required for Th17 cell-mediated pathology in a mouse model ofpsoriasis-like skin inflammation. J Clin Invest 2008;118: 597-607.
312. Dahl CA, Schall RP, He HL, Cairns JS. Identification of a novelgene expressed in activated natural killer cells and T cells. J Immunol1992; 148: 597-603.
313. Shioya M, Nishida A, Yagi Y, Ogawa A, Tsujikawa T, Kim-Mitsuyama S, et al. Epithelial overexpression of interleukin-32alpha in inflammatory bowel disease. Clin Exp Immunol2007;149:480-6.
314. Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA. Interleukin-32: A cytokine and inducer of TNF alpha. Immunity 2005; 22: 131-42.
315. Goda C, Kanaji T, Kanaji S, Tanaka G, Arima K, Ohno S, et al. Involvement of IL-32 in activation-induced cell death in T cells. IntImmunol 2006;18: 233-40.
316. Klunker S, Trautmann A, Akdis M, Verhagen J, Schmid-Grendelmeier P, Blaser K, et al. A second step of chemotaxis aftertransendothelial migration: Keratinocytes undergoing apoptosis releaseIFN-gamma-inducible protein 10, monokine induced by IFNgamma, and IFN-gamma-inducible alpha-chemoattractant for Tcell chemotaxis toward epidermis in atopic dermatitis. J Immunol2003; 171: 1078-84.
317. Basinski TM, Holzmann D, Eiwegger T, Zimmermann M, KlunkerS, Meyer N, et al. Dual nature of T-cell-epithelium interaction inchronic rhinosinusitis. J Allergy Clin Immunol 2009; 124: 74-80, e1-8.
318. Baurecht H, Irvine AD, Novak N, Illig T, Bühler B, Ring J, et al. Toward a major risk factor for atopic eczema: Meta-analysis offilaggrin polymorphism data. J Allergy Clin Immunol 2007; 120:1406-12.
319. th Ed. Chap. 62. Adkinson NF, Bochner BS, Busse WW, et al. Eds. St. Louis, MO: Mosby, 2009;1083-99.
320. Scholoss OM. Allergy to common foods. Trans Am Pediatr Soc1915; 27: 62-8.
321. Ferreira MA. Cytokine expression in allergic inflammation: Systematicreview of in vivo challenge studies. Mediators Inflamm2003; 12: 259-67.
322. Kobayashi Y. The role of chemokines in neutrophil biology. FrontBiosci 2008; 13: 2400-7.
323. Suzukawa M, Iikura M, Koketsu R, Nagase H, Tamura C, KomiyaA, et al. An IL-1 cytokine member, IL-33, induces human basophilactivation via its ST2 receptor. J Immunol 2008; 181: 5981-9.